WO1994015600A1 - Application of riluzole as a radiorestorer - Google Patents
Application of riluzole as a radiorestorer Download PDFInfo
- Publication number
- WO1994015600A1 WO1994015600A1 PCT/FR1994/000002 FR9400002W WO9415600A1 WO 1994015600 A1 WO1994015600 A1 WO 1994015600A1 FR 9400002 W FR9400002 W FR 9400002W WO 9415600 A1 WO9415600 A1 WO 9415600A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- riluzole
- pharmaceutically acceptable
- application
- acceptable salts
- useful
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present invention relates to a new therapeutic application of riluzole (6-trifluoromethoxy-2-amino-benzothiazole) or the pharmaceutically acceptable salts of this compound.
- Riluzole is useful as an anticonvulsant, anxiolytic and hypnotic drug (patent EP 50551), in the treatment of schizophrenia (EP 305276), in the treatment of sleep disorders and depression (EP 305277), in the treatment of cerebrovascular disorders and as an anesthetic (EP 282971).
- Radioremediation is useful in X-ray therapy, particularly in the treatment of cancer and against other sources of harmful radiation such as those encountered by people in areas bordering on nuclear explosions.
- the activity of the product has been demonstrated on the rhinencephalon of young rats subjected to a global gamma irradiation.
- the irradiation is carried out using a gamma ray source, Cobalt 60.
- the animals used are male rats of Sprague Dawley strain weighing 28 to 33 g aged 15 days which are placed in an aerated plexiglass containment box undergoing a rotation of 180 ° in order to carry out global and homogeneous irradiations in a single dose of 1 , 5 and 2.5 Gy with a dose rate of 0.2 Gy per minute.
- the survival time between irradiation and sacrifice is 6 hours. All the animals are fixed by intra-aortic infusion of a fixing liquid composed of 1% paraformaldehyde, 1% glutaraldehyde and 0.05% calcium chloride in a 0.4M phosphate buffer of pH 7.3.
- the product to be studied is administered intraperitoneally at doses of 1, 2, 4 and 8 mg / kg 20 minutes after irradiation (at the start of pycnosis).
- salts with mineral acids such as hydrochloride, sulfate, nitrate, phosphate or organic salts such as acetate, propionate, succinate, oxalate, benzoate, fumarate, maleate, methanesulfonate, isethionate, theophillin- acetate, salicylate, phenolphthalinate, methylene-bis- ⁇ -oxynaphthoate or substitution derivatives of these derivatives.
- mineral acids such as hydrochloride, sulfate, nitrate, phosphate or organic salts such as acetate, propionate, succinate, oxalate, benzoate, fumarate, maleate, methanesulfonate, isethionate, theophillin- acetate, salicylate, phenolphthalinate, methylene-bis- ⁇ -oxynaphthoate or substitution derivatives of these derivatives.
- the medicaments consist of at least riluzole in free form or in the form of an addition salt with a pharmaceutically acceptable acid, in the pure state or in the form of a composition in which it is associated with any other pharmaceutical product. compatible, may be inert or physiologically active.
- the medicaments according to the invention can be used orally or parenterally.
- solid compositions for oral administration tablets, pills, powders (gelatin capsules, cachets) or granules can be used.
- the active principle according to the invention is mixed with one or more inert diluents, such as starch, cellulose, sucrose, lactose or silica, under a stream of argon.
- These compositions can also comprise substances other than diluents, for example one or more lubricants such as magnesium stearate or talc, a dye, a coating (dragees) or a varnish.
- compositions for oral administration there can be used pharmaceutically acceptable solutions, suspensions, emulsions, syrups and elixirs containing inert diluents such as water, ethanol, glycerol, vegetable oils or paraffin oil .
- inert diluents such as water, ethanol, glycerol, vegetable oils or paraffin oil .
- These compositions can include substances other than diluents, for example wetting, sweetening, thickening, flavoring or stabilizing products.
- the sterile compositions for parenteral administration can preferably be aqueous or non-aqueous solutions, suspensions or emulsions.
- solvent or vehicle water, propylene glycol, polyethylene glycol, vegetable oils, in particular olive oil, injectable organic esters, for example ethyl oleate or other organic solvents can be used. suitable.
- These compositions can also contain adjuvants, in particular wetting agents, isotonizers, emulsifiers, dispersants and stabilizers. Sterilization can be done in several ways, for example by aseptic filtration, by incorporating sterilizing agents into the composition, by irradiation or by heating. They can also be prepared in the form of sterile solid compositions which can be dissolved at the time of use in sterile water or any other sterile injectable medium.
- the doses depend on the desired effect, on the duration of the treatment and on the route of administration used; they are generally between 50 and 800 mg per day orally for an adult with unit doses ranging from 25 to 200 mg of active substance and between 25 and 600 mg per day intravenously for an adult with unit doses ranging from 12.5 to 200 mg of active substance.
- the doctor will determine the appropriate dosage based on age, weight and all other factors specific to the subject to be treated.
- Tablets containing 50 mg of active product having the following composition are prepared according to the usual technique:
- capsules containing 50 mg of active product having the following composition are prepared:
- a solution for injection containing 10 mg of active product having the following composition is prepared:
- the invention also relates to the process for the preparation of medicaments useful as radiorestorators, comprising mixing riluzole or the pharmaceutically acceptable salts of this compound with one or more compatible and pharmaceutically acceptable diluents and / or adjuvants.
- the invention also relates to a method of treating mammals and, in particular, humans requiring radioremediation comprising the administration of an effective amount of riluzole or the pharmaceutically acceptable salts of this compound.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Toxicology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Plural Heterocyclic Compounds (AREA)
- Motorcycle And Bicycle Frame (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Dental Preparations (AREA)
- Optical Fibers, Optical Fiber Cores, And Optical Fiber Bundles (AREA)
- Luminescent Compositions (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Description
APPLICATION DU RILUZOLE COMME RADIORESTAURATEUR APPLICATION OF RILUZOLE AS A RADIORESURATOR
La présente invention concerne une nouvelle application thérapeutique du riluzole (trifluorométhoxy-6 amino-2 benzothiazole) ou les sels pharmaceutiquement acceptables de ce composé.The present invention relates to a new therapeutic application of riluzole (6-trifluoromethoxy-2-amino-benzothiazole) or the pharmaceutically acceptable salts of this compound.
Le riluzole est utile comme médicament anticonvulsivant, anxiolytique et hypnotique (brevet EP 50551), dans le traitement de la schizophrénie (EP 305276), dans le traitement des troubles du sommeil et de la dépression (EP 305277), dans le traitement des désordres cérébrovasculaires et comme anesthésique (EP 282971).Riluzole is useful as an anticonvulsant, anxiolytic and hypnotic drug (patent EP 50551), in the treatment of schizophrenia (EP 305276), in the treatment of sleep disorders and depression (EP 305277), in the treatment of cerebrovascular disorders and as an anesthetic (EP 282971).
II a maintenant été trouvé de manière surprenante que ce composé peut aussi être utilisé comme radiorestaurateur.It has now surprisingly been found that this compound can also be used as a radio restaurant.
La radiorestauration est utile dans la thérapie aux rayons X notamment dans le traitement des cancers et contre les autres sources de radiations nuisibles telles que celles rencontrées par les personnes dans les zones limitrophes des explosions nucléaires.Radioremediation is useful in X-ray therapy, particularly in the treatment of cancer and against other sources of harmful radiation such as those encountered by people in areas bordering on nuclear explosions.
L'activité du produit a été mise en évidence sur le rhinencéphale de jeune rat soumis à une irradiation gamma globale.The activity of the product has been demonstrated on the rhinencephalon of young rats subjected to a global gamma irradiation.
L'irradiation s'effectue au moyen d'une source de rayons gamma, Cobalt 60.The irradiation is carried out using a gamma ray source, Cobalt 60.
Les animaux utilisés sont des rats mâles de souche Sprague Dawley pesant 28 à 33 g âgés de 15 jours qui sont placés dans une boite de contention aérée en plexiglass subissant une rotation de 180° afin de réaliser des irradiations globales et homogènes en dose unique de 1,5 et 2,5 Gy dont le débit de dose est de 0,2 Gy par minute. Le délai de survie entre l'irradiation et le sacrifice est de 6 heures. Tous les animaux sont fixés par perfusion intra-aortique d'un liquide fixateur composé de 1% de paraformaldéhyde, 1% de glutaraldéhyde et 0,05% de chlorure de calcium dans un tampon phosphate 0,4M de pH 7,3. Pour éviter la coagulation, on injecte 0,04 ml d'héparine dans le ventricule et 0,3 ml de nitrite de sodium à 1 % pour débarasser les vaisseaux des hématies. Les animaux sont anesthésiés par injection intrapéritonéale de Pentobarbital sodique à 3%. Les animaux sont ensuite couchés sur le dos et fixés sur la table d'opération. La cage thoracique est ouverte et maintenue béante à l'aide de 2 clamps. Le coeur est ainsi dégagé, la pointe du ventricule gauche est incisée, la canule de perfusion introduite jusqu'au début de la crosse de l'aorte et clampée. L'oreillette droite est incisée et la perfusion est effectuée. Le passage du liquide de perfusion est assuré par gravité. Après la perfusion, la tête de l'animal est coupée et le cerveau est prélevé, immergé dans le liquide fixateur et conservé une nuit à 4°C.The animals used are male rats of Sprague Dawley strain weighing 28 to 33 g aged 15 days which are placed in an aerated plexiglass containment box undergoing a rotation of 180 ° in order to carry out global and homogeneous irradiations in a single dose of 1 , 5 and 2.5 Gy with a dose rate of 0.2 Gy per minute. The survival time between irradiation and sacrifice is 6 hours. All the animals are fixed by intra-aortic infusion of a fixing liquid composed of 1% paraformaldehyde, 1% glutaraldehyde and 0.05% calcium chloride in a 0.4M phosphate buffer of pH 7.3. To avoid clotting, 0.04 ml of heparin is injected into the ventricle and 0.3 ml of 1% sodium nitrite to rid the red blood vessels. The animals are anesthetized by intraperitoneal injection of sodium pentobarbital 3%. The animals are then laid on their backs and fixed on the operating table. The rib cage is open and kept open with 2 clamps. The heart is thus released, the tip of the left ventricle is incised, the perfusion cannula inserted until the beginning of the aortic arch and clamped. The right atrium is incised and the infusion is performed. The passage of the infusion liquid is ensured by gravity. After the infusion, the head of the animal is cut off and the brain is removed, immersed in the fixing fluid and stored overnight at 4 ° C.
Le lendemain de la perfusion, on procède à des coupes frontales du gyrus dentatus sous une loupe binoculaire. Les fragments recueillis sont immergés dans le liquide de lavage pendant 5 minutes. Ils sont ensuite déshydratés dans des bains d'alcool de concentration croissante puis inclus dans l'araldite. Les coupes semi-fines de 1 micromètre sont réalisées à l'aide d'un Ultramicrotome Reichert avec des couteaux de verre. Elles sont colorées à chaud avec une solution filtrée de bleu de toluidine à 1% préparée dans du tampon borate à 1% puis observées à l'aide d'un microscope Orthoplan.The day after the infusion, frontal cuts of the gyrus dentatus are made under a binocular magnifying glass. The collected fragments are immersed in the washing liquid for 5 minutes. They are then dehydrated in alcohol baths of increasing concentration and then included in the araldite. The semi-fine sections of 1 micrometer are made using a Reichert Ultramicrotome with glass knives. They are stained hot with a filtered solution of 1% toluidine blue prepared in 1% borate buffer and then observed using an Orthoplan microscope.
L'étude comparative consiste à compter sur 3 coupes non sériées (séparées de 10 micromètre chacune), pour chaque rat et sur un ensemble de 1000 cellules au total (granulaires et subgranulaires). On comptabilise le nombre de cellules pycnotiques puis le nombre de cellules survivantes observées dans cette zone. Ceci permet de calculer le pourcentage de cellules survivantes par rapport au nombre de cellules de la zone (pourcentage de survie = 100 x cellules vivantes / cellules vivantes + cellules pycnotiques).The comparative study consists of counting on 3 non-serial sections (separated by 10 micrometers each), for each rat and on a set of 1000 cells in total (granular and subgranular). The number of pycnotic cells is counted and then the number of surviving cells observed in this area. This makes it possible to calculate the percentage of surviving cells relative to the number of cells in the zone (percentage of survival = 100 x living cells / living cells + pycnotic cells).
Le produit à étudier est administré par voie intrapéritonéale aux doses de 1, 2, 4 et 8 mg/kg 20 minutes après l'irradiation (au début de la pycnose).The product to be studied is administered intraperitoneally at doses of 1, 2, 4 and 8 mg / kg 20 minutes after irradiation (at the start of pycnosis).
Les résultats obtenus sont mentionnés dans les tableaux suivants et montrent que, après traitement avec le produit testé, la dégénérescence neuronale est inférieure par rapport aux témoins irradiés ne recevant pas de produit. ESSAI 1The results obtained are mentioned in the following tables and show that, after treatment with the test product, the neuronal degeneration is lower compared to the irradiated controls not receiving the product. TEST 1
ESSAI 2TEST 2
Comme sels pharmaceutiquement acceptables peuvent être notamment cités les sels d'addition avec les acides minéraux tels que chlorhydrate, sulfate, nitrate, phosphate ou organiques tels que acétate, propionate, succinate, oxalate, benzoate, fumarate, maléate, méthanesulfonate, iséthionate, théophilline-acétate, salicylate, phénolphtalinate, méthylène-bis-β-oxynaphtoate ou des dérivés de substitution de ces dérivés.As pharmaceutically acceptable salts, mention may in particular be made of addition salts with mineral acids such as hydrochloride, sulfate, nitrate, phosphate or organic salts such as acetate, propionate, succinate, oxalate, benzoate, fumarate, maleate, methanesulfonate, isethionate, theophillin- acetate, salicylate, phenolphthalinate, methylene-bis-β-oxynaphthoate or substitution derivatives of these derivatives.
Les médicaments sont constitués par au moins le riluzole sous forme libre ou sous forme d'un sel d'addition avec un acide pharmaceutiquement acceptable, à l'état pur ou sous forme d'une composition dans laquelle il est associé à tout autre produit pharmaceutiquement compatible, pouvant être inerte ou physioiogiquement actif. Les médicaments selon l'invention peuvent être employés par voie orale ou parentérale. Comme compositions solides pour administration orale, peuvent être utilisés des comprimés, des pilules, des poudres (capsules de gélatine, cachets) ou des granulés. Dans ces compositions, le principe actif selon l'invention est mélangé à un ou plusieurs diluants inertes, tels que amidon, cellulose, saccharose, lactose ou silice, sous courant d'argon. Ces compositions peuvent également comprendre des substances autres que les diluants, par exemple un ou plusieurs lubrifiants tels que le stéarate de magnésium ou le talc, un colorant, un enrobage (dragées) ou un vernis.The medicaments consist of at least riluzole in free form or in the form of an addition salt with a pharmaceutically acceptable acid, in the pure state or in the form of a composition in which it is associated with any other pharmaceutical product. compatible, may be inert or physiologically active. The medicaments according to the invention can be used orally or parenterally. As solid compositions for oral administration, tablets, pills, powders (gelatin capsules, cachets) or granules can be used. In these compositions, the active principle according to the invention is mixed with one or more inert diluents, such as starch, cellulose, sucrose, lactose or silica, under a stream of argon. These compositions can also comprise substances other than diluents, for example one or more lubricants such as magnesium stearate or talc, a dye, a coating (dragees) or a varnish.
Comme compositions liquides pour administration orale, on peut utiliser des solutions, des suspensions, des émulsions, des sirops et des élixirs pharmaceutiquement acceptables contenant des diluants inertes tels que l'eau, Péthanol, le glycérol, les huiles végétales ou l'huile de paraffine. Ces compositions peuvent comprendre des substances autres que les diluants, par exemple des produits mouillants, édulcorants, épaississants, aromatisants ou stabilisants.As liquid compositions for oral administration, there can be used pharmaceutically acceptable solutions, suspensions, emulsions, syrups and elixirs containing inert diluents such as water, ethanol, glycerol, vegetable oils or paraffin oil . These compositions can include substances other than diluents, for example wetting, sweetening, thickening, flavoring or stabilizing products.
Les compositions stériles pour administration parentérale, peuvent être de préférence des solutions aqueuses ou non aqueuses, des suspensions ou des émulsions. Comme solvant ou véhicule, on peut employer l'eau, le propylèneglycol, un polyéthylèneglycol, des huiles végétales, en particulier l'huile d'olive, des esters organiques injectables, par exemple l'oléate d'éthyle ou d'autres solvants organiques convenables. Ces compositions peuvent également contenir des adjuvants, en particulier des agents mouillants, isotonisants, émulsifiants, dispersants et stabilisants. La stérilisation peut se faire de plusieurs façons, par exemple par filtration aseptisante, en incorporant à la composition des agents stérilisants, par irra¬ diation ou par chauffage. Elles peuvent également être préparées sous forme de compositions solides stériles qui peuvent être dissoutes au moment de l'emploi dans de l'eau stérile ou tout autre milieu stérile injectable.The sterile compositions for parenteral administration can preferably be aqueous or non-aqueous solutions, suspensions or emulsions. As solvent or vehicle, water, propylene glycol, polyethylene glycol, vegetable oils, in particular olive oil, injectable organic esters, for example ethyl oleate or other organic solvents can be used. suitable. These compositions can also contain adjuvants, in particular wetting agents, isotonizers, emulsifiers, dispersants and stabilizers. Sterilization can be done in several ways, for example by aseptic filtration, by incorporating sterilizing agents into the composition, by irradiation or by heating. They can also be prepared in the form of sterile solid compositions which can be dissolved at the time of use in sterile water or any other sterile injectable medium.
Les doses dépendent de l'effet recherché, de la durée du traitement et de la voie d'administration utilisée; elles sont généralement comprises entre 50 et 800 mg par jour par voie orale pour un adulte avec des doses unitaires allant de 25 à 200 mg de substance active et entre 25 et 600 mg par jour par voie intraveineuse pour un adulte avec des doses unitaires allant de 12,5 à 200 mg de substance active.The doses depend on the desired effect, on the duration of the treatment and on the route of administration used; they are generally between 50 and 800 mg per day orally for an adult with unit doses ranging from 25 to 200 mg of active substance and between 25 and 600 mg per day intravenously for an adult with unit doses ranging from 12.5 to 200 mg of active substance.
D'une façon générale, le médecin déterminera la posologie appropriée en fonction de l'âge, du poids et de tous les autres facteurs propres au sujet à traiter.In general, the doctor will determine the appropriate dosage based on age, weight and all other factors specific to the subject to be treated.
Les exemples suivants illustrent des médicaments selon l'invention :The following examples illustrate medicaments according to the invention:
Exemple AExample A
On prépare, selon la technique habituelle, des comprimés dosés à 50 mg de produit actif ayant la composition suivante :Tablets containing 50 mg of active product having the following composition are prepared according to the usual technique:
- Riluzole 50 mg- Riluzole 50 mg
- Mannitol 64 mg- Mannitol 64 mg
- Cellulose microcristalline 50 mg- Microcrystalline cellulose 50 mg
- Polyvidone excipient 12 mg- Polyvidone excipient 12 mg
- Carboxyméthylamidon sodique 16 mg - Talc 4 mg- Carboxymethyl starch sodium 16 mg - Talc 4 mg
- Stéarate de magnésium 2 mg- Magnesium stearate 2 mg
- Silice colloïdale anhydre 2 mg- Anhydrous colloidal silica 2 mg
- Mélange de méthylhydroxypropylcellulose, polyéthylèneglycol 6000, dioxyde de titane (72-3,5-24,5) q.s.p. 1 comprimé pellicule terminé à 245 mg- Mixture of methylhydroxypropylcellulose, polyethylene glycol 6000, titanium dioxide (72-3,5-24,5) q.s.p. 1 film-coated tablet finished at 245 mg
Exemple BExample B
On prépare, selon la technique habituelle, des gélules dosées à 50 mg de produit actif ayant la composition suivante :Using the usual technique, capsules containing 50 mg of active product having the following composition are prepared:
- Riluzole 50 mg - Cellulose 18 mg- Riluzole 50 mg - Cellulose 18 mg
- Lactose 55 mg- Lactose 55 mg
- Silice colloïdale 1 mg- Colloidal silica 1 mg
- Carboxyméthylamidon sodique 10 mg- Carboxymethyl starch sodium 10 mg
- Talc 10 mg - Stéarate de magnésium 1 mg Exemple C- Talc 10 mg - Magnesium stearate 1 mg Example C
On prépare une solution injectable contenant 10 mg de produit actif ayant la composition suivante :A solution for injection containing 10 mg of active product having the following composition is prepared:
- Riluzole 10 mg - Acide benzoïque 80 mg- Riluzole 10 mg - Benzoic acid 80 mg
- Alcool benzylique 0,06 cm3- Benzyl alcohol 0.06 cm3
- Benzoate de sodium 80 mg- Sodium benzoate 80 mg
- Ethanol à 95 % 0,4 cm3- 95% ethanol 0.4 cm3
- Hydroxyde de sodium 24 mg - Propylène glycol 1,6 cm3- Sodium hydroxide 24 mg - Propylene glycol 1.6 cm3
L'invention concerne également le procédé de préparation de médicaments utiles comme radiorestaurateurs consistant à mélanger le riluzole ou les sels pharmaceutiquement acceptables de ce composé avec un ou plusieurs diluants et/ou adjuvants compatibles et pharmaceutiquement acceptables.The invention also relates to the process for the preparation of medicaments useful as radiorestorators, comprising mixing riluzole or the pharmaceutically acceptable salts of this compound with one or more compatible and pharmaceutically acceptable diluents and / or adjuvants.
L'invention concerne également une méthode de traitement des mammifères et, notamment, de l'homme nécessitant une radiorestauration comprenant l'administration d'une quantité efficace de riluzole ou des sels pharmaceutiquement acceptables de ce composé. The invention also relates to a method of treating mammals and, in particular, humans requiring radioremediation comprising the administration of an effective amount of riluzole or the pharmaceutically acceptable salts of this compound.
Claims
Priority Applications (12)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP51574194A JP3262275B2 (en) | 1993-01-07 | 1994-01-03 | Application of riluzole to promote post-irradiation recovery. |
| SK868-95A SK279777B6 (en) | 1993-01-07 | 1994-01-03 | Application of riluzole in the preparation of drugs having radiorestoring properties |
| EP94903934A EP0678022B1 (en) | 1993-01-07 | 1994-01-03 | Application of riluzole as a radiorestorer |
| RU95116449A RU2142801C1 (en) | 1993-01-07 | 1994-01-03 | Agent for radioprotection after irradiation and method of preparing composition showing radioprotective property |
| DE69400908T DE69400908T2 (en) | 1993-01-07 | 1994-01-03 | USE OF RILUZOL FOR PROTECTION AGAINST RADIATION DAMAGE |
| AU58187/94A AU675281B2 (en) | 1993-01-07 | 1994-01-03 | Application of riluzole as a radiorestorer |
| US08/446,733 US5656647A (en) | 1993-01-07 | 1994-01-03 | Application of riluzole for promoting restoration following radiation |
| KR1019950702792A KR100298806B1 (en) | 1993-01-07 | 1994-01-03 | Pharmaceutical composition containing rilusol to promote recovery after irradiation |
| PL94309593A PL309593A1 (en) | 1993-01-07 | 1994-01-03 | Application of rilusole as a radiorestaurantor |
| CA002152280A CA2152280C (en) | 1993-01-07 | 1994-01-03 | Use of riluzole as a radiorestorer |
| NO952308A NO307204B1 (en) | 1993-01-07 | 1995-06-12 | Use of riluzole in the manufacture of medications in the treatment of radiation damage |
| GR960402005T GR3021604T3 (en) | 1993-01-07 | 1996-11-14 | Application of riluzole as a radiorestorer. |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR93/00073 | 1993-01-07 | ||
| FR9300073A FR2700116B1 (en) | 1993-01-07 | 1993-01-07 | Application of anti-convulsants as radioprotective agents. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1994015600A1 true WO1994015600A1 (en) | 1994-07-21 |
Family
ID=9442861
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/FR1994/000002 Ceased WO1994015600A1 (en) | 1993-01-07 | 1994-01-03 | Application of riluzole as a radiorestorer |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US5656647A (en) |
| EP (1) | EP0678022B1 (en) |
| JP (1) | JP3262275B2 (en) |
| KR (1) | KR100298806B1 (en) |
| AT (1) | ATE145135T1 (en) |
| AU (1) | AU675281B2 (en) |
| CA (1) | CA2152280C (en) |
| CZ (1) | CZ284327B6 (en) |
| DE (1) | DE69400908T2 (en) |
| DK (1) | DK0678022T3 (en) |
| ES (1) | ES2093515T3 (en) |
| FR (1) | FR2700116B1 (en) |
| GR (1) | GR3021604T3 (en) |
| HU (1) | HU217131B (en) |
| IL (1) | IL108283A (en) |
| MX (1) | MX9400288A (en) |
| NO (1) | NO307204B1 (en) |
| PL (1) | PL309593A1 (en) |
| RU (1) | RU2142801C1 (en) |
| SK (1) | SK279777B6 (en) |
| WO (1) | WO1994015600A1 (en) |
| ZA (1) | ZA9427B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6660757B2 (en) | 1998-12-15 | 2003-12-09 | Aventis Pharmaceuticals Inc. | Use of riluzole in the treating acoustic traumas |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0050551A1 (en) * | 1980-10-17 | 1982-04-28 | Pharmuka Laboratoires | Medicament containing 2-amino-6-trifluoro-methoxy benzothiazole |
| SU1109392A1 (en) * | 1983-03-01 | 1984-08-23 | Ордена Трудового Красного Знамени Институт Химии И Химической Технологии Ан Литсср | Process for preparing aromatic thiopropanesulfonic acids or their salts |
| EP0282971A2 (en) * | 1987-03-16 | 1988-09-21 | Warner-Lambert Company | Substituted 2-aminobenzothiazoles and derivatives useful as cerebrovascular agents |
| WO1991017984A1 (en) * | 1990-05-18 | 1991-11-28 | Rhone-Poulenc Rorer S.A. | (3-alkylthio propyl)-3 benzothiazoline derivatives, preparation thereof and drugs containing said derivatives |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4918090A (en) * | 1988-01-25 | 1990-04-17 | Warner-Lambert Company | Substituted 2-aminbenzothiazoles and derivatives useful as cerebrovascular agents |
| US5236940A (en) * | 1988-12-15 | 1993-08-17 | Rhone-Poulenc Sante | Pharmaceutical compositions, 2-benzothiazolamine derivatives, and their preparation |
| US5240948A (en) * | 1989-12-13 | 1993-08-31 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | 3-(3-alkylthiopropyl)benzothiazoline derivatives, their preparation and the medicament containing them |
-
1993
- 1993-01-07 FR FR9300073A patent/FR2700116B1/en not_active Expired - Fee Related
-
1994
- 1994-01-03 AU AU58187/94A patent/AU675281B2/en not_active Ceased
- 1994-01-03 PL PL94309593A patent/PL309593A1/en unknown
- 1994-01-03 WO PCT/FR1994/000002 patent/WO1994015600A1/en not_active Ceased
- 1994-01-03 RU RU95116449A patent/RU2142801C1/en not_active IP Right Cessation
- 1994-01-03 US US08/446,733 patent/US5656647A/en not_active Expired - Lifetime
- 1994-01-03 DE DE69400908T patent/DE69400908T2/en not_active Expired - Lifetime
- 1994-01-03 ES ES94903934T patent/ES2093515T3/en not_active Expired - Lifetime
- 1994-01-03 JP JP51574194A patent/JP3262275B2/en not_active Expired - Fee Related
- 1994-01-03 EP EP94903934A patent/EP0678022B1/en not_active Expired - Lifetime
- 1994-01-03 HU HU9502062A patent/HU217131B/en not_active IP Right Cessation
- 1994-01-03 DK DK94903934.1T patent/DK0678022T3/en active
- 1994-01-03 SK SK868-95A patent/SK279777B6/en not_active IP Right Cessation
- 1994-01-03 CZ CZ951763A patent/CZ284327B6/en not_active IP Right Cessation
- 1994-01-03 CA CA002152280A patent/CA2152280C/en not_active Expired - Fee Related
- 1994-01-03 AT AT94903934T patent/ATE145135T1/en active
- 1994-01-03 KR KR1019950702792A patent/KR100298806B1/en not_active Expired - Fee Related
- 1994-01-04 ZA ZA9427A patent/ZA9427B/en unknown
- 1994-01-05 MX MX9400288A patent/MX9400288A/en unknown
- 1994-01-06 IL IL108283A patent/IL108283A/en not_active IP Right Cessation
-
1995
- 1995-06-12 NO NO952308A patent/NO307204B1/en not_active IP Right Cessation
-
1996
- 1996-11-14 GR GR960402005T patent/GR3021604T3/en unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0050551A1 (en) * | 1980-10-17 | 1982-04-28 | Pharmuka Laboratoires | Medicament containing 2-amino-6-trifluoro-methoxy benzothiazole |
| SU1109392A1 (en) * | 1983-03-01 | 1984-08-23 | Ордена Трудового Красного Знамени Институт Химии И Химической Технологии Ан Литсср | Process for preparing aromatic thiopropanesulfonic acids or their salts |
| EP0282971A2 (en) * | 1987-03-16 | 1988-09-21 | Warner-Lambert Company | Substituted 2-aminobenzothiazoles and derivatives useful as cerebrovascular agents |
| WO1991017984A1 (en) * | 1990-05-18 | 1991-11-28 | Rhone-Poulenc Rorer S.A. | (3-alkylthio propyl)-3 benzothiazoline derivatives, preparation thereof and drugs containing said derivatives |
Non-Patent Citations (2)
| Title |
|---|
| C. MALGOURIS ET AL.: "Riluzole. a novel antiglutamate, prevents memory loss and hippocampal neuronal damage in ischemic gerbils", J. NEUROSCI., vol. 9, no. 11, 1989, pages 3720 - 3727 * |
| DATABASE WPI Week 8511, Derwent World Patents Index; AN 85-067485 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6660757B2 (en) | 1998-12-15 | 2003-12-09 | Aventis Pharmaceuticals Inc. | Use of riluzole in the treating acoustic traumas |
Also Published As
| Publication number | Publication date |
|---|---|
| IL108283A0 (en) | 1994-04-12 |
| AU675281B2 (en) | 1997-01-30 |
| PL309593A1 (en) | 1995-10-30 |
| ATE145135T1 (en) | 1996-11-15 |
| SK86895A3 (en) | 1995-11-08 |
| IL108283A (en) | 1998-02-22 |
| JP3262275B2 (en) | 2002-03-04 |
| FR2700116B1 (en) | 1995-02-03 |
| ES2093515T3 (en) | 1996-12-16 |
| JPH08505377A (en) | 1996-06-11 |
| NO952308L (en) | 1995-06-12 |
| DK0678022T3 (en) | 1996-12-02 |
| GR3021604T3 (en) | 1997-02-28 |
| CZ176395A3 (en) | 1995-12-13 |
| KR960700053A (en) | 1996-01-19 |
| MX9400288A (en) | 1994-07-29 |
| DE69400908T2 (en) | 1997-04-03 |
| RU2142801C1 (en) | 1999-12-20 |
| DE69400908D1 (en) | 1996-12-19 |
| HUT72329A (en) | 1996-04-29 |
| CA2152280A1 (en) | 1994-07-21 |
| HU217131B (en) | 1999-11-29 |
| KR100298806B1 (en) | 2001-11-22 |
| NO952308D0 (en) | 1995-06-12 |
| CA2152280C (en) | 2005-06-28 |
| HU9502062D0 (en) | 1995-09-28 |
| AU5818794A (en) | 1994-08-15 |
| SK279777B6 (en) | 1999-03-12 |
| EP0678022B1 (en) | 1996-11-13 |
| EP0678022A1 (en) | 1995-10-25 |
| ZA9427B (en) | 1994-08-11 |
| FR2700116A1 (en) | 1994-07-08 |
| CZ284327B6 (en) | 1998-10-14 |
| NO307204B1 (en) | 2000-02-28 |
| US5656647A (en) | 1997-08-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0627919B1 (en) | Application of 2-amino 6-trifluoromethoxy benzothiazole (riluzole) for obtaining a drug useful in the treatment of motor neuron diseases | |
| EP0678023B1 (en) | Application of riluzole in the treatment of parkinson's disease and parkinsonian syndromes | |
| EP0687177B1 (en) | Use of lamotrigine for treating aids-related neural disorders | |
| EP0674520A1 (en) | Application of carbamazepine and oxcarbazepine in the treatment of neurological lesions related to traumatic injuries | |
| EP0305276A2 (en) | Use of 2-amino-6-trifluoromethoxybenzothiazole for the preparation of a medicament for the treatment of schizophrenia | |
| FR2619713A1 (en) | APPLICATION OF AMINO-2 TRIFLUOROMETHOXY-6 BENZOTHIAZOLE TO OBTAIN MEDICINE FOR THE TREATMENT OF SLEEP AND DEPRESSION DISORDERS | |
| EP0738147A1 (en) | Application of riluzole in the treatment of mitochondrial diseases | |
| EP0678022B1 (en) | Application of riluzole as a radiorestorer | |
| FR2797399A1 (en) | USE OF CYAMEMAZINE IN THE TREATMENT OF BENZODIAZEPINE WEANING | |
| FR2702149A1 (en) | Application of lamotrigine in the treatment of neuro-AIDS | |
| EP0374042A2 (en) | Use of carbipramine in the preparation of a medicament for the treatment of anxiety and sleeping disorders | |
| FR2774592A1 (en) | APPLICATION OF 2-AMINO-6-TRIFLUOROMETHOXYBENZOTHIAZOLE FOR THE PREVENTION OR TREATMENT OF BRAIN MALFUNCTIONS | |
| FR2702151A1 (en) | Application of anticonvulsants in the treatment of neuro-AIDS | |
| FR2605222A1 (en) | THERAPEUTIC AGENT BASED ON N- (2-HYDROXYETHYL) NICOTINAMIDE FOR THE TREATMENT OF DISORDERS ASSOCIATED WITH CEREBRAL ISCHEMIA | |
| FR2700115A1 (en) | Use of anticonvulsants carbamazepine and oxcarbazepine | |
| FR2700114A1 (en) | Use of the anticonvulsant lamotrigin and its salts |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): AU CA CZ HU JP KR NO PL RU SK UA US |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE |
|
| DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| WWE | Wipo information: entry into national phase |
Ref document number: 08446733 Country of ref document: US |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 1994903934 Country of ref document: EP |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 2152280 Country of ref document: CA |
|
| WWE | Wipo information: entry into national phase |
Ref document number: PV1995-1763 Country of ref document: CZ Ref document number: 86895 Country of ref document: SK |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 1019950702792 Country of ref document: KR |
|
| WWP | Wipo information: published in national office |
Ref document number: 1994903934 Country of ref document: EP |
|
| WWP | Wipo information: published in national office |
Ref document number: PV1995-1763 Country of ref document: CZ |
|
| WWG | Wipo information: grant in national office |
Ref document number: 1994903934 Country of ref document: EP |
|
| WWG | Wipo information: grant in national office |
Ref document number: PV1995-1763 Country of ref document: CZ |